Dystonia Table 1: Classification of Dystonia I.
Primary Dystonia (Formerly Idiopathic): Dystonia is the Only Symptom; No Neurodegeneration or Acquired Etiology is Present
1. Early Onset: Onset in Childhood or Adolescence, Usually Limb Onset with Spread to Other Regions - DYT1
- Other genes not yet identified (e.g. autosomal recessive DYT2).
2. Mixed Phenotype: Primarily Adolescent and Early Adult Onset, Although also with Later Onset, Usually with Onset in Neck, Cranial Muscles, or Arm, with Spread to Other Regions - DYT6 (THAP1): Mennonite kindreds and other families of European ancestry; dysarthria is a common feature
- DYT13 (gene not identified): one Italian family with segmental cervical and cranial muscle involvement
- DYT17 (gene not identified); one Lebanese family
3. Adult Onset (>26 Years of Age), Usually Onset in Neck, Cranial Muscles, or One Arm; Usually Remains Focal or Segmental - DYT7 (gene not identified): in a German family with torticollis - Other genes/causes not yet identified
II. Secondary Dystonia
1. Dystonia-Plus Syndromes: Inherited Syndromes with No Evidence of Neurodegeneration; Features Other than Dystonia are Present Dopa-responsive dystonia (DRD) - Autosomal dominant form due to GTP cyclohydrolase I (GCH1) mutations (DYT5)
- Autosomal recessive forms due to mutations in tyrosine hydroxylase (TH), 6-pyruvoyltetrahydropterin synthase (6-PTPS), sepiapterin reductase
Myoclonus dystonia (MD) - Many familial cases are due to epsilon-sarcoglycan (SGCE) mutations (DYT11)
- DYT15: locus on chromosome 18 in one family; gene not identified
Rapid-onset dystonia-parkinsonism (RDP) - ATP1A3 mutations (DYT12)
2. Inherited Disorders with Dystonia Associated with Neurodegeneration and Other Neurologic Symptoms Autosomal dominant Huntington’s disease (HD) Machado–Joseph’s disease/spinocerebellar ataxia type 3 (SCA3) disease Other SCA subtypes (e.g. SCA2, 6, 17) Familial basal ganglia calcifications (Fahr’s) Dentatorubral-pallidoluysia atrophy (DRPLA) Neuroferritinopathy
Autosomal recessive Juvenile Parkinsonism (Parkin) Wilson’s Glutaric acidemia
commonly due to lesions of the basal ganglia, specifically the putamen or globus pallidus. However, the absence of neurodegeneration in primary dystonia, as well as observations that lesions of brain regions other than the basal ganglia can lead to secondary dystonia, have led to the concept of dystonia as a neuro-functional disorder, i.e. a disorder characterized by abnormal connectivity that may occur in a structurally normal appearing brain. Dystonia symptoms may occur, then, due to
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Neurodegeneration with brain iron accumulation 1 Gangliosidoses (GM1, GM2) Metachromatic leukodystrophy Homocystinuria Propionic acidemia Methylmalonic aciduria Dystonic lipidosis/Neimann Pick type C (NPC1) Ceroid-lipofuscinosis Ataxia-telangiectasia (AT) Ataxia with Vitamin E deficiency Recessive ataxia with ocular apraxia Neuroacanthocytosis Neuronal intranuclear inclusion disease (NIID), etc
X-linked recessive Lubag (X-linked dystonia-parkinsonism, DYT3) Lesch–Nyhan syndrome Deafness/dystonia
Pelizaeus–Merzbacher disease Mitochondrial Myoclonic epilepsy with ragged red fibers (MERRF) Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Leber’s disease
3. Dystonia Due to Acquired Causes Perinatal cerebral injury Encephalitis, infectious and post-infectious Paraneoplastic Head trauma Pontine myelinolysis Primary antiphospholipid syndrome Stroke Tumor Multiple sclerosis Cervical cord injury or lesion Peripheral injury Drugs: dopamine receptor blockers Toxins
III. Dystonia as a Feature of Other Movement Disorders 1. Dystonia Due to Degenerative Parkinsonian Disorders Parkinson’s disease (PD)
Progressive supranuclear palsy (PSP) Multisystem atrophy (MSA)
Cortico-basal-ganglionic degeneration (CBGD)
2. Paroxysmal Dyskinesia Disorders Paroxysmal kinesigenic dyskinesia (PKD) (DYT10/episodic kinesigenic dyskinesia 1, EKD2)
Paroxysmal nonkinesigenic dyskinesia (PNKD) (DYT8) Choreoathetosis/spasticity, episodic (CSE) (DYT9)
3. Tics (Dystonic tics)
developmental abnormalities resulting in synaptic dysfunction or increased plasticity of motor circuits; dystonia is therefore considered to be a motor system disorder rather than a disease of a particular motor structure. Accordingly, studies using various investigative tools have yielded evidence of dysfunction in almost every region of the central nervous systm (CNS) involved in motor control and sensorimotor integration, including cortex, brainstem, cerebellum, and spinal cord.2–4
US NEUROLOGY
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